1. Draft Guidance for Industry: Preventive Measures to Reduce the Possible Risk of Transmission of Creutzfeldt-Jakob Disease (CJD) and Variant Creutzfeldt-Jakob Disease (vCJD) by Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps) TSEAC 26 June 2002

2. CJD/vCJD Draft Guidance Background Information Differences between Blood CJD/vCJD Guidance and Tissue Draft Guidance Draft Guidance and Recommendations Committee Considerations

3. Background January 2001 TSEAC Meeting Unanimous agreement that there is a significant risk of transmission of vCJD from HCT/Ps as compared to the risk of vCJD from blood transfusion Greatest risk: dura mater and cornea No reason to believe risk of vCJD less than that for sporadic CJD

4. Background (cont.) January 2001 TSEAC (cont.) Majority agreement that FDA should recommend donor deferral criteria for possible exposure to the BSE agent Exception for Hematopoietic Stem Cells (HSC) should be provided

5. Background (Cont.) January 2001 TSEAC (Cont.) No advice from committee regarding specific deferral criteria Countries Time periods of potential exposure Duration of exposure No vote regarding donor history interview requirement for ALL HCT/P donors

6. Background (cont.) Tissue Draft Guidance published June 2002 Guidance modeled after blood guidance Same criteria used No information available about risk as reduction versus supply for tissues like for blood (i.e. REDS data)

7. Differences between blood Guidance and tissue Draft Guidance No two-phase implementation Exception made for HLA-matched hematopoietic stem cell collection Includes request to submit data to assess the impact of these recommendations on supply

8. Tissue Draft Guidance Background information Establishes regulatory authority Statement of public health concern TSEAC recommendations General information about CJD and vCJD Clinical presentation Diagnosis Epidemic information

9. Tissue Draft Guidance (cont.) Basis for CJD Recommendations Previous recommendations in guidance Discussion of known cases of CJD transmission by tissues (dura mater and cornea)

10. Tissue Draft Guidance (cont.) Basis for vCJD Recommendations Lists 5 currently recognized risks of exposure to BSE agent Includes information to support exposure risks

11. Tissue Draft Guidance (cont.) Recommendations for Donor Eligibility Determine ineligible any donor who: 1. Has been diagnosed with vCJD or any other form of CJD

12. Tissue Draft Guidance (cont.) Determine ineligible any donor who: (cont.) 2. Has been diagnosed with dementia or any degenerative or demyelinating disease of the central nervous system (CNS) or other neurological disease of unknown etiology (tissue from donor with dementia may be acceptable based upon evaluation by the medical director if confirmed by gross and microscopic examination to be caused by CVA, brain tumor, head trauma, or toxic/metabolic and not by TSE)

13. Tissue Draft Guidance (cont.) Determine ineligible any donor who: 3. Is at increased risk for CJD Dura mater transplant recipient Human pituitary-derived growth hormone >/= 1 blood relative with CJD

14. Tissue Draft Guidance (cont.) Determine ineligible any donor who: 4. Spent three months or more cumulatively in the U.K. from 1980 through end of 1996

15. Tissue Draft Guidance (cont.) Determine ineligible any donor who: 5. Is a current or former U.S. military member, civilian military employee, or dependent of military or civilian employee who resided at U.S. military bases in Northern Europe for 6 months or more from 1980 through 1990, or elsewhere in Europe for 6 months or more from 1980 through 1996

16. Tissue Draft Guidance (cont.) Determine ineligible any donor who: 6. Lived cumulatively for 5 years or more in Europe from 1980 until the present (including time spent in the U.K. from 1980-1996)

17. Tissue Draft Guidance (cont.) Determine ineligible any donor who: 7. Received any transfusion of blood or blood components in the U.K. between 1980 and the present 8. Has injected bovine insulin since 1980, unless confirmed not manufactured after 1980 from cattle in the U.K.

18. Tissue Draft Guidance (cont.) All geographical references in the deferral recommendations are defined in the document. e.g. Northern Europe Recognition is given to HLA-matching issues with HSC. If a HSC donor would otherwise be determined ineligible by recommendations 3-8, the risks of using the cells may be outweighed by the benefits. HSC may be collected and stored. Use of the HSCs in this circumstance may be considered an “urgent medical need.”

19. Tissue Draft Guidance (cont.) CJD/vCJD screening questions to be included in the donor’s medical history. Unfamiliarity with term CJD may be taken as a negative response. CJD in blood relative excluded unless: Diagnosis of CJD subsequently found inaccurate The CJD was iatrogenic Lab testing shows donor without mutation associated with familial CJD

20. Tissue Draft Guidance (cont.) HCT/Ps from donors considered ineligible for donation may be retained for nonclinical scientific or educational uses with proper labeling and storage. Industry affected by this draft guidance are encouraged to submit any data they have now, or could obtain through studies, concerning the effect of implementation of these recommendations on the tissue supply.

21. Tissue Draft Guidance (cont.) This is draft guidance and it is not necessary to implement at this time. When a final guidance is issued, there will not be a two step phase-in period as there is for the blood guidance.

22. Charge to TSEAC Comment on recommendations made in the draft guidance. Consider how information can be obtained about the effect of implementing these tissue donor deferral criteria on the tissue supply in the United States.